The present invention relates to benzyloxy cyclopropyl substituted phenyl compounds, compositions containing these compounds and methods for controlling fungi and insects by the use of a fungitoxic or insecticidal amount of these compounds.
It is known that propenoic acids and oxime ethers of certain benzyloxy substituted phenyl compounds are useful as fungicides. The substitution of the phenyl ring by oximes are known in the art (see for example U.S. Pat. No. 5,166,399 and U.S. Pat. No. 5,358,968).
We have discovered phenyl derivatives which possess a substituted cyclopropyl moiety. These novel derivatives also possess fungicidal and insecticidal properties.
The novel benzyloxy substituted phenyl compounds of the present invention have the Formula (I) 
wherein A is N or CH; V is O or NH;
m and n are the integers 0 and 1, provided that m+n is 1;
X is selected from the group consisting of hydrogen, halo, (C1-C4)alkyl, and (C1-C4)alkoxy;
Z is NR5R6, OR5 or CR7R8R9, provided that when Zxe2x95x90OR5, n=O;
R is selected from the group consisting of hydrogen, (C1-C12)alkyl, (C1-C12)alkoxy, halo(C1-C12)alkyl, (C2-C2)alkenyl, halo(C2-C12)alkenyl, (C2-C12)alkynyl, halo(C2-C12)alkynyl, halo(C1-C12)-alkoxy, (C1-C12)alkoxy(C1-C12)alkyl, halo(C1-C12)alkoxy(C1-C12) alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C12)alkyl, (C3-C7)cycloalkyl(C2-C12)alkenyl, (C3-C7)cycloalkyl(C2-C12) alkynyl, (C1-C12)alkyl(C3-C7)cycloalkyl, (C1-C12)alkoxy(C3-C7)cycloalkyl, (C1-C12)alkoxy(C1-C12)alkyl(C3-C7)cycloalkyl, (C2-C12)alkenyl(C3-C7)cycloalkyl, (C2-C12) alkynyl(C3-C7)cycloalkyl, halo(C1-C12)alkyl(C3-C7)cycloalkyl, (C1-C12)alkoxy(C2-C12)alkenyl(C3-C7)cycloalkyl, (C1-C12)alkoxy(C2-C12)alkynyl(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C3-C7)-cycloalkyl, (C1-C12)alkyl(C3-C7)cycloalkyl(C3-C7)cycloalkyl, (C2-C12)alkenyl(C3-C7)cycloalkyl(C3-C7)cycloalkyl, (C2-C12)alkynyl(C3-C7)cycloalkyl(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C12)alkyl(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C2-C12)alkenyl(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C2-C12)alkynyl(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C12) alkoxy(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C12)alkoxy(C1-C12)alkyl(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C12)alkoxy(C2-C12)alkenyl(C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C12) alkoxy(C2-C12)alkynyl(C3-C7)cycloalkyl, aryl, aralkyl, aryl(C3-C7)cycloalkyl, aryl(C3-C7)cycloalkyl(C3-C7)cycloalkyl, (C3-C7)cycloalkylaryl, aryl(C1-C4)alkyl(C3-C7)cycloalkyl, heterocyclic, aryl(C1-C4)alkylheterocyclic, heterocyclic(C1-C4)alkyl, heterocyclic(C3-C7) cycloalkyl, and C(R11)xe2x95x90Nxe2x80x94OR10 provided that when n=1, R and R1 are not both hydrogen;
R1 and R4 are independently selected from the group consisting of hydrogen, halogen, (C1-C12)alkyl, (C1-C12)alkoxy, halo(C1-C12)alkyl, (C2-C12)alkenyl, (C2-C12)alkynyl, (C3-C7)cycloalkyl, cyano, carboxy, (C1-C4)alkoxycarbonyl, (C1-C12)alkylcarbonyl, and aryl;
R2 and R3 are selected such that when taken together R2 and R3 form a (C3-C7)cycloalkyl ring; or are each independently selected from the group consisting of hydrogen, halogen, (C1-C12)alkyl, (C1-C12)alkoxy, halo(C1-C12)alkyl, (C2-C12)alkenyl, (C2-C12)alkynyl, (C3-C7)cycloalkyl, cyano, carboxy, (C1-C4)alkoxycarbonyl, (C1-C12)alkylcarbonyl, and aryl;
R5 and R6 are (C1-C12)alkyl, (C1-C12)alkoxy, halo(C1-C12)alkyl, (C2-C12)alkenyl, halo(C2-C12)alkenyl, (C2-C12)alkynyl, halo(C2-C12)alkynyl, halo(C1-C12)-alkoxy, (C1-C12)alkoxy(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C1-C4)alkoxycarbonyl, (C1-C12)alkylcarbonyl, arylcarbonyl, aryl, aralkyl, heterocyclic and heterocyclic(C1-C4)alkyl;
R7, R8, and R9 are independently selected from the group consisting of hydrogen, (C1-C12)alkyl, (C1-C12)alkoxy, halo(C1-C12)alkyl, (C2-C12)alkenyl, halo(C2-C12)alkenyl, (C2-C12)alkynyl, halo(C2-C12)alkynyl, halo(C1-C12)alkoxy, (C1-C12)alkoxy(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C1-C7)cycloalkyl, cyano, (C1-C4)alkoxycarbonyl, (C1-C12)alkylcarbonyl, arylcarbonyl, aryl, aralkyl, heterocyclic and heterocyclic(C1-C4)alkyl;
R10 is selected from the group consisting of hydrogen, (C1-C12)alkyl, halo(C1-C12)alkyl, (C2-C12)alkenyl, halo(C2-C12)alkenyl, (C2-C12)alkynyl, halo(C2-C12)alkynyl, (C1-C4)alkylcarbonyl, (C1-C4)alkoxycarbonyl, aryl, and aralkyl;
R11 is selected from the group consisting of hydrogen, (C1-C12)alkyl, halo(C1-C12)alkyl, (C3-C7)cycloalkyl, halo(C3-C7)cycloalkyl, (C2-C12)alkenyl, halo C2-C12)alkenyl, (C2-C12)alkynyl, halo(C2-C12)alkynyl, aryl, aralkyl, heterocyclic, and heterocyclic(C1-C4)alkyl.
The aforementioned (C1-C12)alkyl, (C1-C12)alkoxy, (C2-C12)alkenyl, (C2-C12)alkynyl and (C3-C7)cycloalkyl groups may be optionally substituted with up to three substituents selected from the group consisting of halogen, nitro, trihalomethyl and cyano.
Unless otherwise qualified, the term alkyl includes both branched and straight chain alkyl groups from 1 to 12 carbon atoms. Typical alkyl groups are methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, isooctyl, nonyl, decyl, undecyl, dodecyl and the like. The term haloalkyl refers to an alkyl group substituted with 1 to 3 halogens.
Unless otherwise qualified, the term alkoxy includes both branched and straight chain alkyl groups from 1 to 12 carbon atoms containing at least one oxygen atom. Typical alkoxy groups are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy isobutoxyl, t-butoxy, n-pentoxy, isopentoxy, n-hexoxy, n-heptoxy and the like. The term haloalkoxy refers to an alkoxy group substituted with 1 to 3 halogens.
Unless otherwise qualified, the term alkenyl refers to an ethylenically unsaturated hydrocarbon group, straight or branched, having a chain length of 2 to 12 carbon atoms and 1 or 2 ethylenic bonds. The term haloalkenyl refers to an alkenyl group substituted with 1 to 3 halogen atoms. The term alkynyl refers to an unsaturated hydrocarbon group, straight or branched, having a chain length of 2 to 12 carbon atoms and 1 or 2 acetylenic bonds.
The term cycloalkyl refers to a saturated ring system having 3 to 7 carbon atoms.
The term aryl includes phenyl or naphthyl, which maybe substituted with up to three substituents independently selected from the group consisting of halogen, cyano, nitro, trihalomethyl, phenyl, phenoxy, (C1-C6)alkyl, (C1-C4)alkylthio, (C1-C4)alkylsulfoxide, (C1-C6)alkoxy and halo(C1-C4)alkyl.
Typical aryl substituents include but are not limited to 4-chlorophenyl, 4-fluorophenyl, 4-bromophenyl, 2-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2, 4-dibromophenyl, 3, 5-difluorophenyl, 2, 4, 6-trichlorophenyl, 4-methoxyphenyl, 2-chloronaphthyl, 2, 4-dimethoxyphenyl, 4-(trifluoromethyl)phenyl and 2-iodo-4-methylphenyl.
The term heterocyclic refers to a substituted or unsubstituted 5 or 6 membered unsaturated ring containing one, two or three heteroatoms, preferably one or two heteroatoms independently selected from oxygen, nitrogen and sulfur or to a bicyclic unsaturated ring system containing up to 10 atoms including one heteroatom selected from oxygen, nitrogen and sulfur. Examples of heterocycles includes but is not limited to 2-, 3- or 4-pyridinyl, pyrazinyl, 2-, 4-, or 5-pyrimidinyl, pyridazinyl, triazolyl, imidazolyl, 2- or 3-thienyl, 2- or 3-furyl, pyrrolyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, quinolyl and isoquinolyl. The heterocyclic ring may be optionally substituted with up to two substituents independently selected from (C1-C2) alkyl, halogen, cyano, nitro and trihalomethyl.
Unless otherwise qualified, the term aralkyl is used to describe a group wherein the alkyl chain is from 1 to 10 carbon atoms and can be branched or straight chain, preferably a straight chain, with the aryl portion, as defined above, forming a terminal portion of the aralkyl moiety. Typical aralkyl moieties are optionally substituted benzyl, phenethyl, phenpropyl and phenbutyl moieties. Typical benzyl moieties are 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 4-trifluoromethylbenzyl, 2, 4-dichlorobenzyl, 2, 4-dibromobenzyl, 2-methylbenzyl, 3-methylbenzyl, and 4-methylbenzyl. Typical phenethyl moieties are 2-(2-chlorophenyl)ethyl, 2-(3-chlorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(2-fluorophenyl)ethyl, 2-(3-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(2-25 methylphenyl)ethyl, 2-(3-methylphenyl)-ethyl, 2-(4-methylphenyl)ethyl, 2-(4-trifluoromethylphenyl)ethyl, 2-(2-methoxyphenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 2-(2, 4-dichlorophenyl)ethyl, 2-(3, 5-dimethoxyphenyl)ethyl. Typical phenpropyl moieties are 3-phenylpropyl, 3-(2-chloro-phenyl)propyl, 3-(3-chlorophenyl)propyl, 3-(4-chlorophenyl)propyl, 3-(2, 4-dichlorophenyl)-propyl, 3-(2-fluorophenyl)propyl, 3-(3-fluorophenyl)propyl, 3-(4-fluorophenyl)propyl, 3-(2-methylphenyl)propyl, 3-(3-methylphenyl)propyl, 3-(4-methylphenyl)ethyl, 3-(2-methoxy-phenyl)propyl, 3-(3-methoxyphenyl)propyl, 3-(4-methoxyphenyl)propyl, 3-(4-trifluoromethyl-phenyl)propyl, 3-(2, 4-dichlorophenyl)propyl and 3-(3, 5-dimethoxyphenyl)propyl. Typical phenbutyl moieties include are 4-phenylbutyl, 4-(2-chlorophenyl)butyl, 4-(3-chlorophenyl)butyl, 4-(4-chlorophenyl)butyl, 4-(2-fluorophenyl)butyl, 4-(3-fluorophenyl)butyl, 4-(4-fluorophenyl)-butyl, 4-(2-methylphenyl)butyl, 4-(3-methylphenyl)butyl, 4-(4-methylphenyl)butyl, 4-(2, 4-dichlorophenyl)butyl, 4-(2-methoxphenyl)butyl, 4-(3-methoxyphenyl)butyl and 4-(4-methoxy-phenyl)butyl.
Halogen or halo is meant to include iodo, fluoro, bromo and chloro moieties.
Because of the Cxe2x95x90N double bonds the novel compounds of the general Formula I may be obtained in preparation as E/Z isomeric mixtures. These isomers can be separated into individual components by conventional means. The cyclopropanes of Formula I may be obtained in preparation as cis- and trans- isomeric mixtures which can be separated into individual components by conventional means. Both the individual isomeric compounds and mixtures thereof form subjects of the invention and can be used as fungicides.
A preferred embodiment of this invention are the compounds, enantiomorphs and salts of Formula (I) where is X is hydrogen and R is (C1-C12)alkyl, (C2-C12)alkenyl, (C2-C12)alkynyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C12)alkyl, (C3-C7)cycloalkyl(C2-C12)alkenyl, (C1-C12)alkyl(C3-C7)cycloalkyl, (C2-C12)alkenyl(C3-C7)cycloalkyl, phenyl substituted with preferably one or two substituents independently selected from halo, trihalomethyl, cyano, (C1-C4)alkyl, (C1-C4)alkylthio, (C1-C4)alkoxy or phenyl, where the OCH2(2-substitutedphenyl) is bonded at the meta position to the (Cxe2x95x90Nxe2x80x94Z)n-cyclopropyl ring substituent of the phenyl ring as shown in Formula II. 
A more preferred embodiment of this invention are the compounds, enantiomorphs, salts and complexes of Formula (II) where n is zero, m is one, Z is OR5, R is (C3-C7)cycloalkyl, phenyl substituted with preferably one or two substituents independently selected from halo or trihalomethyl, R1, R2, R3 and R4 are hydrogen and A is N and V is NH. The preferred geometry when A is N is the E isomer as shown in Formula III. 
Typical compounds encompassed by the present invention of Formula I (X=H, R1xe2x95x90R2xe2x95x90R3xe2x95x90R4=H) and include those compounds presented in Table 1 of Formula II, III and IV (Z is OR5, n=0, m=1) where R and R5 are defined in Table 1.
Further typical compounds described by the present invention are described in the following tables.
Table II: Compounds 2.01 to 2.115 are Compounds of Table 1 of Formula II, III, IV where V=O and A is N.
Table III:
Compounds 3.01 to 3.115 are Compounds of Table 1 of Formula II, III, IV where V=NH and A is N.
Typical compounds encompassed by the present invention of Formula I (X=H, R1xe2x95x90R2xe2x95x90R3xe2x95x90R4=H) and include those compounds presented in Table IV of Formula V, VI and VII (Z is Nxe2x80x94R5R6, n=0, m=1) where R and R5 are defined in Table IV.
Further typical compounds described by the present invention are described in the following tables.
Table V:
Compounds 5.01 to 5.110 are Compounds of Table IV of Formula V, VI, VII where V=O and A is N
Table VI:
Compounds 6.01 to 6.110 are Compounds of Table IV of Formula V, VI, VII where V=NH and A is N
Typical compounds encompassed by the present invention of Formula I (X=H, R1xe2x95x90R2xe2x95x90R3xe2x95x90R4=H) and include those compounds presented in Table VII of Formula VIII, IX and X (Z is Nxe2x80x94R5R6, n=1, m=0) where R and R5 are defined in Table VII.
Further typical compounds described by the present invention are described in the following tables.
Table VIII:
Compounds 8.01 to 8.110 are Compounds of Table VII of Formula VIII, IX, X where V=O and A is N.
Table IX:
Compounds 9.01 to 9.110 are Compounds of Table VII of Formula VIII, IX, X where V=NH and A is N.
Typical compounds encompassed by the present invention of Formula I (X=H) include those compounds presented in Table X of Formula XI, XII and XIII where one of R1 or R2 or R3 or R4 is not H, Z can be Nxe2x80x94R5R6, or Z can be OR5 if n=0 (and m=1), where R, R1, R2, R3, R4 and Z are defined in Table X.
Further typical compounds described by the present invention are described in the following tables.
Table XI:
Compounds 11.01 to 228 are Compounds of Table X of Formula XI, XII, XIII where V=O and A is N
Table XII:
Compounds 12.01 to 228 are Compounds of Table X of Formula XI, XII, XIII where V=NH and A is N
Typical compounds encompassed by the present invention of Formula I (X=R1xe2x95x90R2xe2x95x90R3xe2x95x90R4=H) include those compounds presented in Table XIII of Formula XIV, XV and XVI (Z is Nxe2x95x90C(R7R8R9, n or m=1 and n+m=1) where R, R7, R8, and R9 are defined in Table XIII .
Further typical compounds described by the present invention are described in the following tables.
Table XIV: Compounds 14.01 to 228 are Compounds of Table XIII of Formula XIV, XV, XVI where V=O and A is N
Table XV: Compounds 15.01 to 228 are Compounds of Table XIII of Formula XIV, XV, XVI where V=NH and A is N
As used in Tables I to XV Ph is understood to be phenyl.
Scheme A describes the general preparation of compounds of the Formula (I). where A is CH or N, and V is 0. The cyclopropyl substituted phenols (XVII) are reacted with the appropriately substituted benzyl bromide derivative (XVIII). Cyclopropyl substituted phenols represented by the general formula (XVII) are treated, at room temperature, with an appropriate base to form an anion, followed by the addition of the benzyl bromide. Typical bases employed are metal hydrides such as sodium hydride, alkoxides such as sodium methoxide and hydroxide bases such as sodium or potassium hydroxide and alkali bases such as sodium or potassium carbonate. Typical solvents employed with hydride bases are N, N-dimethylformamide (DMF) and tetrahydrofuran (THF); with hydroxide bases DMF, THF, methyl ethyl ketone (MEK) and acetone and with alkali bases solvents such as DMF, acetone, and MEK. 
Scheme B describes the preparation of the compounds of Formula XX (m=O and n=1) of Tables VII, VIII, X. XI, XIII and XIV. Compounds of Formula XXI where A is CH and V is 0 (Tables VII, X, XIII) are prepared by alkylation of the cyclopropane intermediate XIX with methyl E-xcex1-(2-bromomethylphenyl)-xcex2-methoxyacrylate. XVIIII, in the presence of a base, preferably NaOH or KOH, in a solvent, preferably acetone or methyl ethyl ketone. Methyl E-xcex1-(2-bromomethylphenyl)-xcex2-methoxyacrylate, XVIIII, as a single E isomer, can be prepared in two steps from 2-methylphenylacetate as described previously in U.S. Pat No. 4,914,128, columns 3-4. As is shown in Scheme B compounds of Formula XXII (m=0 and n=1, A is N and V is O of Tables VIII, XI, XIV) are prepared by the reaction with methyl E-2-(bromomethyl)-phenylglyoxylate O-methyloxime, XVIIIII, in the presence of a base, preferably NaOH or KOH, in a solvent, preferably acetone or methyl ethyl ketone. Methyl 2-(bromomethyl)phenylglyoxylate O-methyloxime can be prepared as described in U.S. Pat. No. 4,999,042, columns 17-18 and U.S. Pat. No. 5,157,144, columns 17-18. Methyl 2-(bromomethyl)phenylglyoxylate O-methyl oxime is prepared from methyl 2-methylphenylacetate by treatment with an alkyl nitrite under basic conditions to provide after methylation, methyl 2-methylphenylglyoxalate O-methyl oxime which can also be prepared from methyl 2-methylphenylglyoxalate by treatment with 2-hydroxylamine hydrochloride and methylation or by treatment with methoxylamine hydrochloride. 
As shown in scheme C compounds of formula XXIII where m=0 and n=1 and A is N and V is NH) prepared by the aminolysis of oximinoacetate XXII (A is N and V is O). The aminolysis of oximinoacetate to oximinoacetamides has been described in U.S. Pat. No. 5,185,342, cols. 22, 48 and U.S. Pat. No. 57, 5,221,691, cols. 26-27 and U.S. Pat. No. 5,407,902, col. 8. For example, compounds of Tables VIII, XI and XIV where A is N and Z is O are treated with 40% aqueous methylamine in methanol to provide compounds of Tables IX, XII and XV where V is NH. Alternatively, as is shown in scheme C intermediate cyclopropane XIX is reacted with N-methyl (E)-2-methoxyimino-2-[2-(bromomethyl)phenyl]acetamide, XXI, in the presence of a base such as an hydroxide base preferably in a solvent such as acetone or methyl ethyl ketone to directly provide compounds of formula XXIII. N-methyl (E)-2-methoxy-imino-2-[2-(bromomethyl)phenyl]-acetamide is described in U.S. Pat. No. 5,387,714, col. 13. 
Scheme D describes the preparation of the compounds of formula XXV (m=1 and n=0) of Tables 1, II, IV, V, X, XI, XIII and XIV. The alkylations of the cyclopropane intermediates XXIV with the benzyl bromide XVIIII, where A is CH and V is O, are compounds of Tables I, IV, X and XIII. Also shown in Scheme D is the preparation of compounds of formula XXV (m=1 and n=0) where A is N and V is O and are compounds of Tables II, V, XI and XIV. 
As shown in scheme E, compounds of formula XXVII (where m=1 and n=0 and A is N and V=NH) are prepared by the aminolysis of oximinoacetate XXVI Is (A is N and V is O) as described for scheme C. For example, compounds of Tables II, V, XI and XIV where A is N and Z is O are treated with 40% aqueous methylamine in methanol to provide compounds of Tables III, VI, XII and XV where V is NH. Alternatively, as is shown in scheme E intermediate cyclopropane XXIV is reacted with XXI as described for scheme C to directly provide compounds of formula XXVII of Tables III, VI, XII and XV. 
The substituted cyclopropyl derivatives of the general formula XVII can be obtained, as shown in scheme F, by reacting the corresponding cyclopropane ketones and aldehydes (XXVIII) with NH2OR5, NH2NR5R6 or NH2R7R8R9 from room temperature to reflux, preferably at room temperature, in an appropriate solvent such as methanol or ethanol in the presence of an appropriate alkali such as sodium hydroxide, potassium carbonate or pyridine. A general description of the synthesis of oximes, imines and hydrazones from carbonyl compounds is described in March, Advanced Organic Chemistry, 4th Ed, pp. 894 and 904-907 and references therein. The compounds of the general formula XVII and specifically XIX and XXIV when obtained as a mixture of syn or anti oxime isomers can be separated into individual isomers and alkylated as described in Schemes A to E. When a mixture of compounds of the general formula XVII and specifically XIX and XXIV are used in Scheme A to E the compounds of the formula I can be separated into their individual isomers by conventional chromatographic techniques 
The general synthesis of the cyclopropanes of the general Formula XXVIII are described in EP 0889024. The cyclopropanes of the general Formula XXVIII can be prepared by conventional techniques as shown in scheme G. The unsaturated intermediate XXIX (Scheme J) is reacted with a sulfur ylide, prepared from a dimethylsulfoxonium salt in the presence of a base, resulting in the substituted acyl cyclopropanes, XXVIII. The chemistry of sulfur ylides is described in Trost and Melvin, Sulfur Ylids, Academic Press, New York, N.Y. 1975 and in Block, Reactions of Organosulfur Compounds, pp. 91-123, Academic Press, New York, N.Y. 1978. Typical reaction conditions for sulfur ylide formation to from a dimethylsulfoxonium salt utilizes bases such as hydroxides, metal hydrides and alkoxides in solvents such as dimethoxyethane, dimethylsulfoxide and water depending on the base employed. The reactions are conducted from 0 to 20xc2x0 C. preferably from 10-15xc2x0 C. and preferably with alkali metal hydroxides in dimethylsulfoxide. Typically dimethylsulfoxonium methylide is prepared from trimethylsulfoxonium iodide in dimethylsulfoxide in the presence of powdered sodium hydroxide at room temperature. The unsaturated ketones or aldehydes, XXIX are added drop wise to the ylide and stirred at room temperature. 
Scheme H describes the preparation of benzoylcyclopropanes of the Formula XXVIIII where n=1 and m=0, by reaction of the enone, XXIXI, with the sulfur ylid (CH3)2S(O)xe2x95x90CR2R3. Additionally, in Scheme H is shown the preparation of the acylcyclopropane phenols of Formula XXVIIIII where n=0 and m=1 by reaction of the enone, XXIXII with the ylide (CH3)2S(O)=CR2R3. 
Scheme I describes the preparation of benzoylcyclopropanes (XXVIII) and cyclopropylimines (XVII) where R1-R4 are hydrogen. When n=1 and m=0 the cyclopropane XVIIIII is prepared from the benzoylcyclopropanes XXVIIIIII which is prepared from the unsaturated intermediate XXIXIII via the sulfur ylide as described in Scheme G. The enones XXIXIII are prepared by conventional techniques from the aldehydes RCHO and the isomeric substituted hydroxy-acetophenones. When n=0 and m=1 the cyclopropane XVIIIV is prepared from the acylcyclopropane XXVIIIIV which is prepared from the unsaturated intermediate XXIXIV as described in Scheme G. The enones XXIXIV are prepared by conventional techniques from the ketones RCOCH3 and the isomeric substituted hydroxybenzaldehydes. 
Alternatively the cyclopropyl ketones XXVIII, specifically XXVIIII and XXVIIIIII, can be prepared from cyclopropyl nitrites XXXI which are prepared via cyclopropanation of the acrylonitriles XXX as is described in Scheme J. The acrylonitriles starting materials (XXX), shown in Scheme J can be prepared by conventional synthetic methods as described in March, Advanced Organic Chemistry, 4th Ed, pp. 937-955 and references therein. For the benzoylcyclopropanes, XXVIIII, where n=1 and m=0 the nitrile derivative R4CH2CN is condensed with the ketone or aldehyde RCOR, in the presence of a base to provide the acrylonitriles XXXI. Typically the nitrile is dissolved in a solvent such as ethanol and water to which is added the aldehyde or ketone followed by a base. Typical bases used can be alkali metal hydroxides, such as barium, potassium or sodium hydroxide and the mixture is stirred typically at ambient temperature. 
For the arylcyclopropanes, XXVIIIII, where n=0 and m=1 the nitrile derivative R1CH2CN is condensed with the arylketone or benzaldehyde (HO)PhCOR4 in the presence of a base to provide the acrylonitriles XXXII. The acrylonitriles XXXI and XXXII are treated as is described in Scheme G with a sulfur ylide to provide the cyclopropyl nitrites XXXII and XXXIII. The cyclopropyl nitrites are transformed to the cyclopropyl ketones by organometallic addition to the nitrite followed by hydrolysis. For example when n=1 and m=0 the Grignard reagent is an aryl Grignard reagent and when n=0 and m=1 a Grignard reagent or an organolithium reagent, RLi adds to the nitrite functionality to provide the ketones XXVIIII and XXVIIII, respectively. The addition reaction to nitrites are described in March, Advanced Organic Chemistry, 4th Ed, pp.935-936 and references cited therein.
Scheme K describes the preparation of the compounds of Formula XXIV where n=0 and m=1 in which R is C(R11)xe2x95x90Nxe2x80x94OR10. The ketones, XXVIIIV, wherein R10 is not H, or the aldehydes R10 is H, are reacted with an alkyl nitrite such as t-butylnitrite or isoamylnitrite under basic conditions to provide the corresponding xcex1-oximino cyclopropylketones XXXII. Typically the cyclopropyl ketone or aldehydes in a solvent such as t-butanol and the alkyl nitrite, typically t-butylnitrite, is added to a solution t-butanol containing a base such as potassium t-butoxide and is stirred at room temperature. The xcex1-hydroxyimino cyclopropylketones XXXII are alkylated with R10X to provide the xcex1-(substituted)oximino cyclopropylketones XXXIII. Finally, the intermediate XXXIV is formed by reaction with NH2OR5, NH2NR5R6 or NH2R7R8R9 as is described previously in Scheme F. 
Alternatively the compounds of Formula I can be prepared as described in Scheme L.
The compounds of Formula XXXV which are described in EP 0889024 can be reacted directly with NH2OR5, NH2NR5R6 or NH2R7R8R9 as is described previously in Scheme F to provide compounds of the Formula I. 
The compounds of this invention can be made according to the following procedures: